Advertisement

Fortschritte in der Impfstoffentwicklung gegen Tuberkulose

  • Jürgen Hess
  • H. E. Kaufmann
Chapter

Zusammenfassung

Die effektive Kontrolle der Tuberkulose, die noch immer zu den weltweit bedeutendsten Infektionskrankheiten zählt, wird am ehesten durch eine Kombination aus Chemotherapie und Impfung erreicht. Mit BCG steht zwar ein Impfstoff zur Verfügung, der jedoch den Ausbruch der Lungentuberkulose bei Erwachsenen als häufigste Erkrankungsform nicht verhindern kann. Die Entwicklung eines neuen Impfstoffs gegen Tuberkulose ist daher vorrangiges Ziel. Da die Infektabwehr von unterschiedlichen T-Zellpopulationen getragen wird, muß angestrebt werden, die für den Schutz optimale Kombination zu stimulieren. Ein Drittel der Weltbevölkerung ist mit dem Erreger bereits infiziert, so daß möglicherweise zwei Impfstoffe benötigt werden: einer zur Bekämpfung der bereits etablierten Infektion (Infektionstherapie) und ein anderer zur raschen Erregerabwehr nach Erstkontakt (Infektionsprävention). Derzeit werden unterschiedliche Impfstoffkandidaten entwickelt, deren Erfolgschancen noch schwer abzuschätzen sind.

Schlüsselwörter

Tuberkulose Impfung BCG 

Progress in vaccine development against tuberculosis

Summary

Tuberculosis is, on a global level, still one of the most important infectious diseases. Effective control of tuberculosis could probably be achieved by a combination of chemotherapy and vaccination. Although a vaccine (BCG) is available, it cannot prevent the development of tuberculosis of the lungs in adults as the most frequent disease manifestation. The development of a new vaccine against tuberculosis therefore remains a primary goal. Because the immune defense against M. tuberculosis depends on different T-cell subpopulations, the optimal combination has to be stimulated to achieve protection. Because one third of the world population is already infected with M. tubercolosis, possibly two vaccines are needed: one therapeutic vaccine to fight an already established infection and a preventive vaccine. Currently different vaccine candidates are under development. It is still to early to predict, which may be successful.

Key words

Tuberculosis Vaccine BCG 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. 1.
    The world health report (1999) Making a difference. ISBN 92 41561947, ISSN 1020-3311.Google Scholar
  2. 2.
    Grange JM (1996) Epidemiological aspects of drug resistance. ImMycobacteria and human disease. Arnold, London, pp 124–125.Google Scholar
  3. 3.
    Sturgill-Koszycki S, Schlesinger PH, Chakraborty P, Haddix PL, Collins HL, Fok AK, Allen RD, Gluck SL, Heuser J, Russell DG (1994) Lack of acidification in Mycobacterium phagoso-mes produced by exclusion of the vesicular proton-ATPase. Science 263:678–681.PubMedCrossRefGoogle Scholar
  4. 4.
    Deretic V, Fratte RA (1999) Mycobacterium tuberculosis phagosome. Mol Micro bio I 31:1603–1609.Google Scholar
  5. 5.
    Hmama Z, Gabathuler R, Jeffries WA, de Jong G, Reiner NE (1998) Attenuation of HLA-DR expression ny mononuclear phagocytes infected with Mycobacterium tuberculosis is related to intracellular sequestration of immature class II heterodimers. J Immunol 161:4882–4893.PubMedGoogle Scholar
  6. 6.
    Pancholi P, Mirza A, Bhardwaj N, Steinman RM (1993) Sequestration from immune CD4 T cells of mycobacteria growing in human macrophages. Science 260:984–986.PubMedCrossRefGoogle Scholar
  7. 7.
    Kaufmann SHE (1993) Tuberculosis: The role of the immune response. The Immunologist 1:109–114.Google Scholar
  8. 8.
    Mutis T, Comelisse YE, Ottenhoff TH (1993) Mycobacteria induce CD4T cells that are cytotoxic and display Thi-like cytokine secretion profile: heterogeneity in cytotoxic activity and cytokine secretion levels. EurJ Immunol 23:2189–2195.CrossRefGoogle Scholar
  9. 9.
    Kumararatne DS, Pithie AS, Drysdale P, Gaston JSH, Kiessling R (1990) Specific lysis of mycobacterial antigen-bearing macrophages by class II MHC-restricted polyclonal T cell lines in healthy donors or patients with tuberculosis. Clin Exp Immunol 80:314–323.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Turner J, Dockrell HM (1996) Stimulation of human peripheral blood mononuclear cells with live Mycobacterium bovis BCG activates cytolytic CD8 T cells in vitro. Immunology 87:339–342.PubMedCrossRefGoogle Scholar
  11. 11.
    Schaible UE, Collins H, Kaufmann SHE (1999) Confrontation between intracellular bacteria and the immune system. Advances in Immunology 71:267.PubMedGoogle Scholar
  12. 12.
    Canaday DH, Ziebold C, Noss EH, Chervenak KA, Harding CV, Boom WH (1999) Activation of human CD8 ocßtcr cells by Mycobacterium tuberculosis via an alternate class I MHC antigen-processing pathway. J Immunol 162:372–379.PubMedGoogle Scholar
  13. 13.
    Lalvani A, Brookes R, Wilkinson RJ, Malin AS, Pathan AA, Andersen P, Dockrell H, Pasvol G, Hill AV (1998) Human cytolyticand interferon gamma-secreting CD8 T lymphocytes specific for Mycobacterium tuberculosis. Proc NatlAcad Sci USA 95:270–275.CrossRefGoogle Scholar
  14. 14.
    Lewinsohn DM, Alderson MR, Briden AL, Riddell SR, Reed SG, Grabstein KH (1998) Characterization of human CD8 T cells reactive with Mycobacterium tuberculosis-infected antigen-presenting cells. J Exp Med 187:1633–1640.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Stenger S, Mazzaccaro RJ, Uyemura K, Cho S, Barnes PF, Rosat J-P, Sette A, Brenner MB, Porcelli SA, Bloom BR., Modlin RL (1997) Differential effects of cytolytic T cell subsets on intracellular infection. Science 276:1684–1687.PubMedCrossRefGoogle Scholar
  16. 16.
    Kaufmann SHE (1996) y/d and other unconventional T lymphocytes: What do they see and what do they do? Proc Natl Acad Sci USA 93:2272–2279.PubMedCrossRefGoogle Scholar
  17. 17.
    Porcelli SA (1995) The CD1 family: a third lineage of antigen-presenting molecules. Adv Immunol 59:1–98.PubMedCrossRefGoogle Scholar
  18. 18.
    Stenger S, Hanson DA, Teitelbaum R, Dewan P, Niazi KR, Froelich CJ, Ganz T, Thoma-Uszynski S, Melian A, Bogdan C. Porcelli SA. Bloom BR. Krensky AM. Modlin RL (1998) An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 282:121–125.PubMedCrossRefGoogle Scholar
  19. 19.
    Calmette A, Guerin C, Nègre L, Boquet A (1927) Sur la vaccination prevente des enfants nouveaunes contre la tuberculose par le BCG.Annlnst Pasteur 3:201.Google Scholar
  20. 20.
    Huebner RE (1996) BCG vaccination in the control of tuberculosis. In: Shinnick TM (ed) Current Topics in Microbiology and Immunology: Tuberculosis. Springer, Berlin, pp 263–279.Google Scholar
  21. 21.
    Coldlitz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, Mosteller F (1994) Efficacy of BCG vaccine in the prevention of tuberculosis. JAMA 271:698–702.CrossRefGoogle Scholar
  22. 22.
    Maharais GG, Sabo PJ, Hickey MJ, Singh DC, Stover CK (1996) Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M.bovis. J Bacteriol 178:1274–1282.Google Scholar
  23. 23.
    Behr MA, Wilson MA, Gill WP, Salamon H, Schoolnik GK, Rane S, Small PM (1999) Comparative genomics of BCG vaccine by whole-genome DNA microarray. Science 284:1520–1523.PubMedCrossRefGoogle Scholar
  24. 24.
    Hess J, Kaufmann SHE (1993) Vaccination strategies against intracellular microbes. FEMSMicrobiol Immunol 7:95–103.Google Scholar
  25. 25.
    Kaufmann SHE, Andersen P (1998) Immunity to Mycobacteria with emphasis on tuberculosis: implications for rational design of an effective tuberculosis vaccine. In: Liew FY, Cox FEG (eds) Immunology of intracellular parasitism. Chem Immunol 70:21–59.Google Scholar
  26. 26.
    Cole ST et al (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537–544.PubMedCrossRefGoogle Scholar
  27. 27.
    Jungblut PR, Schaible UE, Mollenkopf H-J, Zimny-Arndt U, Raupach B, Mattow J, Halada P, Lamer S, Hagens K, Kaufmann SHE (1999) The comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis BCG strains: towards functional gnomics of microbial pathogen. Mol Microbiol (im Druck).Google Scholar
  28. 28.
    Handfield M, Levesque RC (1999) Strategies for isolation of in vivo expressed genes from bacteria. FEMS Microbiol Rev 23:69–91.PubMedCrossRefGoogle Scholar
  29. 29.
    Baldwin SL, D’Souza C, Roberts AD, Kelly BP, Frank AA, Lui MA, Ulmer JB, Huygen K, McMurray D, Orme IM (1998) Evaluation of new vaccines in the mouse and guinea pig model of tuberculosis. Infect Immun 66:2951–2959.PubMedCentralPubMedGoogle Scholar
  30. 30.
    Kamath AT, Feng CG, MacDonald M, Briscoe H, Britton WJ (1999) Differential protective efficacy of DNA vaccines expressing secreted proteins of Mycobacterium tuberculosis. Infect Immun 67:1702–1707.PubMedCentralPubMedGoogle Scholar
  31. 31.
    Tascon RE, Colston MJ, Ragno S et al (1996) Vaccination against tuberculosis by DNA injection. Nat Med 2:888–892.PubMedCrossRefGoogle Scholar
  32. 32.
    Huygen K, Content J, Denis O, Montgomery DL et al (1996) Immunogenicity and protective efficacy of tuberculosis DNA vaccine. Nat Med 2:893–898.PubMedCrossRefGoogle Scholar
  33. 33.
    Tanghe A, Lefèvre P, Denis P, D’Souza S, Braibant M, Lozes E, Singh M, Montgomery D, Content J, Huygen K (1999) Immunogenicity and protective efficacy of tuberculosis DNA vaccines encoding putative phosphate transport receptors.J Immunol 162:1113–1119.PubMedGoogle Scholar
  34. 34.
    Denis O, Tanghe A, Palfliet K Jurion F, van den BergTP, Vanonckelen A, Ooms J, Saman E, Ulmer JB, Content J, Huygen K (1998) Vaccination with plasmid DNA encoding mycobacteria I antigen 85 A stimulates a CD4 and CD8T-CGII epitopic repertoire broader than that stimulates by Mycobacterium tuberculosis H37Rv infection. Infect Immun 66:1527–1533.PubMedCentralPubMedGoogle Scholar
  35. 35.
    Barry MA, Lai WC, Johnston SA (1995) Protection against mycoplasma infection using expression-library immunization. Nature 377:632–635.PubMedCrossRefGoogle Scholar
  36. 36.
    Horwitz MA, Lee B-WE, Dillon BJ, Harth G (1995) Protective immunity against tuberculosis induced by vaccination with major extracellular proteins against Mycobacterium tuberculosis. Proc Natl Acad Sci USA 92:1530–1534.PubMedCrossRefGoogle Scholar
  37. 37.
    Walsh GP Jan EV, delà Cruz EC, Abalos RM, Villahermosa LG, Young U, Cellona RV, Nazareno JB, Horwitz MA (1996) The Philippine cynomolgus monkey (Macaca fasicularis) provides a new nonhuman primate model of tuberculosis that resembles human disease. Nat Med 2:430–436.PubMedCrossRefGoogle Scholar
  38. 38.
    Venkataprasad N, Coombes AGA, Singh M, Rohde M, Wilkinson K, Hudecz F, Davis SS, Vordermeier HM (1999) Induction of cellular immunity to a mycobacterial antigen adsorbed on lamellar particles of lactide polymers. Vaccine 17:1814–1819.PubMedCrossRefGoogle Scholar
  39. 39.
    Shiver JW, Ulmer, JB, Donnelly JJ, Liu MA (1996) Naked DNA vaccination. In: Kaufmann SHE (ed) Concepts in vaccine development. Walter deGruyter, Berlin New York, pp 423–436.Google Scholar
  40. 40.
    Pelicic V, Jackson M, Reyrat J-M, Jacobs WRJr, Gicquel B, Guilhot C (1997) Efficient allelic exchange and transposon mutagenesis in Mycobacterium tuberculosis. Proc Natl Acad Sci USA 94:10955–10960.PubMedCrossRefGoogle Scholar
  41. 41.
    Berthet F-X, Lagranderie M, Gounon P, Laurent-Winter C, Ensergueix D, Chavarot P Jhouron F, Maranghi E, Pelicic V, Portnoi D, Marchai G, Gicquel B (1998) Attenuation of virulence by disruption of the Mycobacterium tuberculosis erp gene. Science 282:759–762.PubMedCrossRefGoogle Scholar
  42. 42.
    Yuan Y, Crane DD, Simpson RM, Zhu YQ, Hickey MJ, Sherman DR, Barry CE 3rd (1998) The 16-kDa alpha-crystallin (Acr) protein of Mycobacterium tuberculosis is required for growth in macrophages. Proc Natl Acad Sci USA 95:9578–9583.PubMedCrossRefGoogle Scholar
  43. 43.
    Guleria I, Teitelbaum R, McAdam RA, Kalpana G, Jacobs WR Jr, Bloom BR (1996) Auxotrophic vaccines for tuberculosis. Nat Med 2:334–337.PubMedCrossRefGoogle Scholar
  44. 44.
    Murray PJ, Aldovini A, Young RA (1996) Manipulation and potentiation of anti-mycobacterial immunity using recombinant BCG secreting cytokines. Proc Natl Acad Sci USA 93:934–939.PubMedCrossRefGoogle Scholar
  45. 45.
    Hess J, Miko D, Catic A, Lehmensiek V, Russell DG, Kaufmann SHE (1998) Mycobacterium bovis bacille Calmette-Guérin strains secreting listeriolysin of Listeria monocyto-genes. Proc Natl Acad Sci USA 95:5299–5304.PubMedCrossRefGoogle Scholar
  46. 46.
    Zhu X, Venkataprasad N, Ivanyi J, Vordermeier HM (1997) Vaccination with recombinant vaccinia viruses protects mice against Mycobacterium tuberculosis. Immunology 92:6–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Hess J, Kaufmann SHE (1999) Live antigen carriers as tools for improved anti-tuberculosis vaccines. FEMS Immunology and Medical Microbiology 23:165–173.PubMedGoogle Scholar
  48. 48.
    Crowle AJ (1988) Immunization against tuberculosis: what kind of vaccine? Infect Immun 56:2769–2773.PubMedCentralPubMedGoogle Scholar
  49. 49.
    Lowrie DB, Tascon RE, Bonato VLD, Lima VMF et al (1999) Therapy of tuberculosis in mice by DNA vaccination. Nature (im Druck).Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • Jürgen Hess
    • 1
  • H. E. Kaufmann
    • 1
  1. 1.Abteilung für ImmunologieMax-Planck-Institut für InfektionsbiologieBerlinDeutschland

Personalised recommendations